The field of the invention is the control of tachycardia, including fibrillation, and arrhythmias, particularly the control of atrial fibrillation and ventricular tachycardia.
Tachycardia is the rapid beating of the heart, caused by abnormalities in any part of the heart, for example the atria, Purkinje system, or ventricles. Often, the extremely rapid beating of the heart is uncoordinated, and leads to fibrillation or flutter. These conditions occur after myocardial infarctions, for example, or in various pathological conditions, such as a dilated heart, blockage of the Purkinje system, or following chemical therapies (e.g., epinephrine) or repetitive stimulation. Atrial flutter often becomes atrial fibrillation within a few days or weeks, and leads to a complete failure of the atria to pump blood.
Atrial fibrillation is the most frequent tachycardia in patients. It most frequently occurs in patients over the age of 60 years, and affects over 8% of patients with cardiovascular disease and people older than 80 years (1, 2). Chronic atrial fibrillation doubles mortality (3), mostly due to an increased risk of stroke as well as other cardiovascular complications. Among other risk factors, congestive heart disease imposes the highest risk for developing atrial fibrillation (4.5-5.9 fold) (4). Therefore, restoration of normal sinus rhythm by pharmacological or electrical cardioversion is attempted in many patients with atrial fibrillation. Unfortunately, atrial fibrillation recurrence rates one year after successful cardioversion are high (75% without antiarrhythmic drug prophylaxis and 50% with aggressive antiarrhythmic medication; (5)). Moreover, the likelihood of cardioversion success is low in patients with chronic atrial fibrillation lasting longer than 2 years or who have enlarged atria (6). In many of these patients, therapy is directed toward ventricular rate control during atrial fibrillation in order to stabilize cardiac function. However, in patients with concomitant heart failure, drugs that slow the ventricular rate during atrial fibrillation may further depress ventricular contractility and cause arterial hypotension or be of limited use due to side effects.
Like atrial fibrillation, ventricular tachycardia can lead to fibrillation, which leads to failure of the ventricles to pump blood. Unlike atrial fibrillation, ventricular fibrillation cannot be compensated for by the rest of the heart and rapidly leads to sudden death if not reversed. Ventricular fibrillation is a common cause of death in patients (7). For example, patients who survive myocardial infarction often remain at risk for reentrant ventricular tachycardia. The sympathetic and parasympathetic nerves (autonomic innervation) of the heart influence susceptibility to spontaneous arrhythmias. Sympathetic stimulation can increase the risk of fatal arrhythmias during ischemic events and parasympathetic stimulation can decrease the risk (8). Current efforts to control this excess sympathetic tone include administration of .beta.-adrenergic blocking drugs and surgical sympathectomy (9). Problems with these methods include contraindications for drug therapy in patients who are sensitive to the negative inotropic effects of .beta.-adrenergic blockade and the inherent risks of thoracic surgery, which in this case also include pulmonary complications, injury to the brachial plexus, and upper extremity paresthesias.
Another common measure used to control atrial or ventricular tachycardia is ablation or modification of the His bundle or atrioventricular node and ablation of atrial or ventricular foci. Such ablation may abolish a tachycardia or slow the ventricular response during atrial fibrillation by blocking impulse conduction across the atrioventricular node. Ablation can be performed by introduction of a catheter into the heart through the venous system and subsequent ablation of the tissue.
In 1973, Lazzara and Scherlag reported that electrical stimulation of parasympathetic cardiac nerves at the junction of the right atrium and the inferior vena cava close to the coronary sinus ostium selectively prolonged atrio-ventricular (AV) conduction time (10). Chen et al. showed control of ventricular rate during atrial fibrillation by short bursts of stimulation to parasympathetic nerves in the fat pads to the AV node, but this method can lead to unwanted stimulation of myocardial muscle, and stimulation times are necessarily very brief because the electrode cannot be stably maintained in the appropriate location. Most recently, Reek et al. (12) reported that stimulation of the parasympathetic nerve fibers in the RPA with a conventional electrode catheter decreased the sinus rate in sheep. In addition, electrical stimulation of parasympathetic nerves either during coronary artery bypass grafting operation (CABG) (13) or after CABG operation (14) have demonstrated that parasympathetic fibers innervating the sinus and atrioventricular node can also be stimulated in humans. The stimulation electrodes, however, were only temporarily fixed at the outer surface of the heart or superior vena cava. Chiou et al. demonstrated that extracardiac electrical stimulation of parasympathetic fibers in fat pad between the superior vena cava, the aorta, and adjacent to the right pulmonary artery, diminished AV nodal conduction during sinus rhythm (15). These results required a thoracotomy. Most recently, Thompson and coworker reported that endovascular electrical stimulation of parasympathetic fibers in the superior vena cava with a conventional electrode catheter slows the sinus rate (16).